Handling-habituation prevents the effects of diazepam and alprazolam on brain serotonin levels in rats.

In two different experiments, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in rats, using HPLC with electrochemical detection, in 3 brain regions (hippocampus, cerebral cortex and hypothalamus) after acute i.p. treatment with diazepam (4 mg/kg), alprazolam (1.25 mg/kg) or vehicle. In the first experiment, rats received the acute treatment 30 min before they were sacrificed. In the second, the animals were previously habituated to handling (involving the maneuvers of injecting and sacrificing at the guillotine) daily for 15 days, before the acute administration of the drugs. Results of the acute treatment alone showed a significant increase in 5-HT levels in hippocampus and cerebral cortex, and a decrease in hypothalamus, but not differences in 5-HIAA levels, for the diazepam- and alprazolam-treated groups. After handling-habituation, no effect in the monoamine or metabolite levels appeared when the rats were treated with diazepam or alprazolam. The results are discussed in relation to the emotional changes induced by the handling procedure, and for possible connections between the mechanisms of action of handling-habituation and benzodiazepine treatments at CNS level.